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- Title
Cyclin D2 Is Required for Beta Cell Expansion in Animal Models of Insulin Resistance.
- Authors
Georgia, Senta K.; Kulkarni, Rohit N.; Bhushan, Anil
- Abstract
Insulin resistance derives from the pancreas' inability to produce enough insulin to compensate for increased glucose load coupled with decreased peripheral and/or hepatic insulin sensitivity. Mice that lack insulin receptor substrate 1 (irs1) suffer from insulin resistance, but do not develop overt diabetes because of compensatory increase in beta cell mass that leads to hyperinsulinema. To address the molecular basis of the compensatory mechanism that leads to beta cell mass expansion in the face of increased physiologic demand, we deleted both alleles of cyclin D2 in the irs1-/- background. At 10 weeks of age, cyeD2 -/-irs1-/- are smaller than their single knockout or double heterozygous counterparts and show insulin resistance that is accompanied by glucose intolerance. By 25 weeks, however, cycD2-/-irs1-/-, exhibit severe glucose intolerance, hypoinsulinemia, and have with fasting glucose levels over 350mg/dL, indicating severe diabetes. Histological studies confirm that hypoinsulemia in cycD2-/-irs1-/- animals is due to the inability of beta cells to expand. This study shows that cyclin D2 plays an essential role in the expansion of beta cells in response to increasing metabolic demand This work reinforces the idea that cyclin D2 is a specific target for expansion of beta cell mass, and shows potential as a therapeutic for patients suffering from insulin dependent diabetes.
- Subjects
CYCLINS; PANCREATIC beta cells; INSULIN resistance; GLUCOSE; DIABETES; ANIMALS
- Publication
Diabetes, 2007, Vol 56, pA47
- ISSN
0012-1797
- Publication type
Article